The vascular pathobiology of sickle cell disease undoubtedly is influenced by the status of the vascular endothelial cell. The endothelium participates in numerous aspects of vascular physiology/biology that are of direct relevance to this disease. Despite the likely involvement of the endothelium in sickle disease in general, including in the hemostatic perturbations in this disease, nothing is known about its function in the patient. We propose to attempt to solve this by a novel approach in which we will harvest circulating endothelial cells from sickle cell disease patients (in steady-state and presenting with acute painful crisis) as well as controls. These will be evaluated for their phenotypic character to answer several specific questions. 1. We will quantitate the number of circulating endothelial cells, expecting this to rise in conjunction with acute painful crisis. 2. We will determine whether circulating endothelial cells are actually viable. 3. We will determine whether circulating endothelial cells are microvascular in origin. 4. We will determine whether circulating endothelial cells have a procoagulant phenotype. 5. We will define the complement of surface adhesion receptors on circulating endothelial cells. 6. We will evaluate circulating endothelial cells to see if they have elevated levels of mRNA for endothelin or nitric oxide synthase. 7. We will study selected "positive control" patients who will help define the usefulness of the above measurements made in sickle patients. We expect these studies to provide insight into the status of the vascular endothelium in the sickle patient.